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Murray Edwards College
University of Cambridge

Science issue: The gloopy world of collagen proteins

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    10 Mar

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    Elephants rarely get cancer: less than 5% of captive elephants die of cancer, compared to 20% of humans. Elephant genomes have at least 20 copies of the tumour suppressor, p53, which may explain their low cancer rates relative to humans, who have only one copy. 

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    9B Ying Chow photo1NewsI always find it a little misleading to tell people that I am a chemist; the molecules that I am studying come from biology, while the technique that I use comes from physics. The samples I have investigated included bone, tendon, cartilage, and skin; a diverse variety of materials somehow all made from collagen proteins. Together with a range of other proteins, sugar-like molecules, and sometimes minerals, collagen proteins form the extracellular matrix -- the glue-like matrix in which cells are embedded and organised. However, it is not just a passive scaffold: the cells make attachments to the matrix at an atomic level, and this attachment can trigger different cell behaviours. So what are these atomic-level “hooks” that the cell is seeing? Perhaps a little surprisingly, it is not easy to study the atoms in the extracellular matrix. Since it is a gloopy/grainy, cross-linked, heterogeneous mix of proteins, sugars, and more, there is a mind-boggling variety of different kinds of atoms and molecules within a small piece of tissue. Often, a shortened section of pure collagen-like proteins is studied as a simpler model system. However, what if we could have a technique where we can directly compare healthy tissue and diseased tissue atomically? Perhaps we can understand how the differences in bulk property (e.g. stiffness, brittleness) came about, by understanding the molecular and atomic level organisation (e.g. different compositions, different chemical bonds). Changes in the extracellular matrix occur in many diseases, including diabetes and cancer, but also naturally over time as we age. Much of current treatment focuses upon the cells, or surgically removing diseased tissue, but perhaps there are ways to more effective treatment if we can understand, reverse or even prevent these changes at a tissue level.

    Much of my research is about developing an approach to study tissues in an intact manner at an atomic level. The technique that I use, solid-state nuclear magnetic resonance spectroscopy (ssNMR), can sometimes feel like it is a world apart from biology, full of electronics, pulse programming, and liquid nitrogen. All the machinery is part of an attempt to delicately (well, as delicately as you can with a kilowatt of power) nudge the quantum mechanical states of those atoms within the sample, to find out what bonds those atoms are making, what other atoms are nearby, in order to deduce what molecule that atom is a part of. Interpreting the data is much like solving a logical puzzle, trying to fit all the pieces of information to what we know about the experiment and the sample.

    At the moment, I am trying to work out why some parts of collagen proteins appear to be more flexible than others, which may help cells form attachments onto the collagen matrix. Using ssNMR, I could pick out the flexible atom pairs, which exerted a smaller magnetic (dipolar) effect on each other. As a chemist who is working at the border between disciplines, I am always working with a range of scientists from different backgrounds: cell biologists, biochemists, computational chemists, and even engineers and doctors. It is an enriching experience, full of creative solutions, and even more creative questions. If you are interested to find out more, feel free to ask by email or Twitter! Ying Chow Alumna Further reading: Protein Databank 101 Molecule of the month: Collagen http://pdb101.rcsb.org/motm/4 Molecular Biology of the Cell (Alberts et al, 2002) http://www.ncbi.nlm.nih.gov/books/NBK26810/ The Extracellular Matrix at a Glance (Frantz 2010) http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2995612/?tool=pmcentrez Some introduction to solid-state NMR http://u-of-o-nmr-facility.blogspot.de/2008/03/solution-vs-solid-state-mas-nmr.html http://u-of-o-nmr-facility.blogspot.de/2007/11/magic-angle-spinning.html http://u-of-o-nmr-facility.blogspot.de/2010/03/household-dust-bunnies.html http://u-of-o-nmr-facility.blogspot.de/2011/12/13-c-nmr-of-delicious-christmas-treat.html A set of lectures that give a fuller introduction to NMR http://www-keeler.ch.cam.ac.uk/lectures/Irvine/ https://www.youtube.com/watch?v=nM7jQFhrvR0&list=PLE20foNk9J6L1dh9X27RaPiaul8_7wrAY Part I of our recent attempts to understand collagen flexibility (Part II is being prepared…) http://www.nature.com/articles/srep12556 Twitter handle @selkie_upsilon